title: Occult cardiotoxicity in childhood cancer survivors exposed to anthracycline therapy.
abstract: BACKGROUND
  More than 50% of >270 000 childhood cancer survivors in the United States have been treated with anthracyclines and are therefore at risk of developing cardiotoxicity. Cardiac magnetic resonance (CMR) has demonstrated utility to detect diffuse interstitial fibrosis and changes in regional myocardial function. We hypothesized that CMR would identify occult cardiotoxicity characterized by structural and functional myocardial abnormalities in a cohort of asymptomatic pediatric cancer survivors with normal global systolic function.
  
  
  RESULTS
  Forty-six long-term childhood cancer survivors with a cumulative anthracycline dose ≥200 mg/m(2) and normal systolic function were studied 2.5 to 26.9 years after anthracycline exposure. Subjects underwent transthoracic echocardiography, CMR with routine cine acquisition, tissue characterization, and left ventricular strain analysis using a modified 16-segment model. Extracellular volume was measured in 27 subjects, all of whom were late gadolinium enhancement negative. End-systolic fiber stress was elevated in 45 of 46 subjects. Low average circumferential strain magnitude (εcc) -14.9±1.4; P<0.001, longitudinal strain magnitude (εll) -13.5±1.9; P<0.001, and regional peak circumferential strain were seen in multiple myocardial segments, despite normal global systolic function by transthoracic echocardiography and CMR. The mean T1 values of the myocardium were significantly lower than that of control subjects at 20 minutes (458±69 versus 487±44 milliseconds; P=0.01). Higher mean extracellular volume was observed in female subjects (0.34 versus 0.22; P=0.01).
  
  
  CONCLUSIONS
  Asymptomatic postchemotherapy pediatric patients have abnormal myocardial characteristics and strain parameters by CMR despite normal global cardiac function by standard transthoracic echocardiography and CMR measures.
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology and Radiology.
authors.forename: Olga H
authors.initials: OH
authors.lastname: Toro-Salazar
authors.forename: Eileen
authors.initials: E
authors.lastname: Gillan
authors.forename: Michael T
authors.initials: MT
authors.lastname: O'Loughlin
authors.forename: Georgine S
authors.initials: GS
authors.lastname: Burke
authors.forename: Joanna
authors.initials: J
authors.lastname: Ferranti
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Stainsby
authors.forename: Bruce
authors.initials: B
authors.lastname: Liang
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mazur
authors.forename: Subha V
authors.initials: SV
authors.lastname: Raman
authors.forename: Kan N
authors.initials: KN
authors.lastname: Hor
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D015994:Incidence; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D016277:Ventricular Function, Left / Q000187:drug effects*; D055815:Young Adult
chemical_list: D018943:Anthracyclines
keywords: anthracyclines; cardiotoxicity; magnetic resonance imaging; myocardial strain